Preparation of dabigatran was first described in the document no. WO 9837075; however, this method brings many technological problems, e.g. very complicated purifying operations, problems with low purity of intermediate products and the resulting low yield and low purity of the final product.
One of the advanced intermediates during the production of dabigatran is the substance of formula VI.

The compound of formula VI is prepared by a reaction of substance IV with reagent V as shown in Scheme 1.

The procedure described in WO 9837075 produces compound VI in the form of its base or acetate. Both these products require chromatographic purification, which is very difficult to apply in the industrial scale. This purification method burdens the process economy very much and has a negative impact on the yield.
In the next stage acidic hydrolysis of the nitrile function of compound VI and a reaction with ammonium carbonate is performed to produce the substance of formula VII. The reaction is shown in Scheme 2.

The procedure in accordance with WO 9837075 produces substance VII in the monohydrochloride form.
When reproducing the procedure of WO 9837075 we found out, in line with WO 9837075, that compound VII prepared by this method required subsequent chromatographic purification as it was an oily substance with a relatively high content of impurities. We did not manage to find a solvent that would enable purification of this substance by crystallization.
The last stage is a reaction of intermediate VII with hexyl chloroformate producing dabigatran and its transformation to a pharmaceutically acceptable salt; in the case of the above mentioned patent application it is the methanesulfonate.
However, the method in accordance with WO 9837075 does not make it possible to prepare dabigatran with high purity, which is required in the case of a pharmaceutical substance, and in a yield acceptable in the industrial scale.
The reason is mainly low purity of the intermediate products, which are moreover produced in forms requiring complicated purification with the use of chromatographic methods.